Sodium Hydroxide → 3-Methyl-N-(4-(trifluoromethyl)phenyl)isoxazole-4-carboxamide

HRID 429272Notes

Reaction equation

HRID 429272 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:19])[C:11](=[CH:15][O:16]CC)[C:12]([CH3:14])=O)=[CH:5][CH:4]=1.Cl.[NH2:23]O.[OH-].[Na+]>C(O)C.O>[CH3:14][C:12]1[C:11]([C:10]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:21])([F:20])[F:1])=[CH:4][CH:5]=2)=[O:19])=[CH:15][O:16][N:23]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 534242632-(Ethoxymethylidene)-3-oxo-N-[4-(trifluoromethyl)phenyl]butanamide

Product 1

HCID 98602203-Methyl-N-(4-(trifluoromethyl)phenyl)isoxazole-4-carboxamideYield 8.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

N-[4-(Trifluoromethyl)phenyl]-2-(ethoxymethylene)-acetoacetamide (4 g) is suspended in 10 mL of ethanol treated with 1.5 g of hydroxylamine hydrochloride in 10 mL of water which has been adjusted to pH 5 with sodium hydroxide. The mixture is stirred and warmed to 40° C. for 2 hours, then cooled to room temperature and the precipitate collected by vacuum filtration. Sodium hydroxide (1 g) is added to the filtrate which is stirred for 30 minutes. The mixture is acidified to pH 2 with 6 N hydrochloric acid and the precipitate collected by vacuum filtration. The filtrate is then diluted with 100 mL of water and allowed to stand at 4° C. overnight. The precipitate is collected by vacuum filtration, washed with ethanol:water 2:1 and dried to give 300 mg of crude 3-methyl-4-[4-(trifluoromethyl)phenylaminocarbonyl]isoxazole. The crude is purified on a column of silica gel eluting with ethyl acetate:hexane 1:4 to give 100 mg of 3-methyl-4-[4-(trifluoromethyl)phenylaminocarbonyl]isoxazole, an off-white solid.

Workup

  1. temperaturecooled to room temperature
  2. filtrationthe precipitate collected by vacuum filtration
  3. additionSodium hydroxide (1 g) is added to the filtrate which
  4. stirringis stirred for 30 minutes
  5. filtrationthe precipitate collected by vacuum filtration
  6. additionThe filtrate is then diluted with 100 mL of water
  7. filtrationThe precipitate is collected by vacuum filtration
  8. washwashed with ethanol:water 2:1
  9. customdried

Sources & evidence

ORD record
ord-036072de8bcb4592aa10e9d853631f7a
Source dataset
uspto-grants-2001_11
Patent number
US06316479B1

Reaction notes

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